Inhibition of H3K27 methyltransferase EZH2 enhances osteogenic commitment of human mesenchymal progenitors and Ezh2 inactivation in mouse calvarial cells induces a post-proliferative state concomitant with increased production of a bone-related mineralizing extra-cellular matrix. Overall design: Expression of genes of interest, including Ezh2, was assessed during osteogenic differentiation of human adipose-derived mesenchymal (AMSCs) on plastic (2D) and on porous-sintered titanium discs (3D). We also assessed gene expression when AMSCs were differentiated into the adipogenic lineage. In addition, the effect of GSK126 on osteogenic differentiation of AMSCs was also evaluated. Finally, we compared gene expression in calvarial bones obtained from wild type mice and mice lacking functional Ezh2 in the mesenchymal lineage (Prrx1-Cre, 3 day old female mice).